In Response to: “Efficacy of Elimination Diets in Eosinophilic Esophagitis: A Systematic Review and Meta-analysis”
Authors: Marijn J. Warners, Albert J. Bredenoord
Journal: Clinical Gastroenterology and Hepatology (2023)

We found the systematic review of Mayerhofer et al1Mayerhofer C. et al.Clin Gastroenterol Hepatol. 2023; 21: 2197-2210Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar on the efficacy of elimination diets in eosinophilic esophagitis (EoE) captivating and the study offered a comprehensive review of the existing literature. We wholeheartedly agree that dietary treatment holds immense potential as a sustainable drug-fee treatment for EoE. Nevertheless, we believe that the actual efficacy of dietary treatment in clinical practice is less impressive than the favorable outcomes presented in their review. Presently, dietary treatment is still extremely time consuming, not only for the patients who are on restrictive diets for months, but it also results in considerable costs and pressure on health care systems, including multiple endoscopies with biopsy sampling. Additionally, patient's adherence is challenging, and a small dietary mistake can ruin the effort of months of dietary treatment by leading to a wrong conclusion. Despite these disadvantages, dietary treatment could play a significant role in the treatment of EoE if response rates in clinical practice would indeed be comparable with the 80.8% clinical and 53.8% histologic response rates as described in the recently published review. However, it is likely that these response rates are overestimated. First, most dietary studies are single-armed and noncomparative study designs, have small sample sizes and no mention of handling patients lost to follow-up, with diverse methodologies and varying population characteristics, which makes these studies prone to placebo effects and bias. In their discussion the authors concluded that the effectiveness of dietary treatment is nearly on par with the effectiveness of topical corticosteroid. To date, there have been no randomized controlled trials comparing topical corticosteroids with dietary treatment. However, when comparing the quality of carefully conducted randomized controlled trials assessing topical steroids against placebo with a long follow-up2Straumann A. et al.Gastroenterology. 2020; 159: 1672-1685Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar with many uncontrolled dietary treatment studies, the disparities are substantial. In total Mayerhofer et al1Mayerhofer C. et al.Clin Gastroenterol Hepatol. 2023; 21: 2197-2210Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar included 4 randomized controlled trials of which only 1 was published;3De Rooij W. et al.Neurogastroenterol Motil. 2022; 34e14291Google Scholar the other 3 are still only available as abstracts, which increases the risk of bias because no information was available about the randomization process and the selection of the reported results. In the only published randomized controlled trial complete histologic remission was achieved in only 25% of the patients treated with the 4-food elimination diet, which is considerably lower that their concluded 4-food elimination diet histologic response rates of 49.9%. Among the findings of the review, the outcomes of the targeted elimination diets stood out as particularly unexpected. The systematic analysis reported a pooled histologic response rate of 43%, a surprising finding, considering that most of these test-directed diets were designed relying on the outcomes of IgE-mediated skin prick tests, which correctly identifies food triggers in ≤13%.4Lucendo A. et al.J Allergy Clin Immunol. 2013; 131: 797-804Abstract Full Text Full Text PDF PubMed Scopus (335) Google Scholar,5Philpott H. et al.Aliment Pharmacol Ther. 2016; 44: 223-233Crossref PubMed Scopus (89) Google Scholar Therefore, new testing approaches using CD4+ T-cell proliferation were designed with even poorer histologic response rates of 21%.6Dellon A. et al.Clin Transl Gastroenterol. 2019; 10e00099Crossref PubMed Scopus (25) Google Scholar Additionally most targeted elimination diet studies were retrospective, with sample sizes nearly all <20 patients. In the recently published systematic review, a combined histologic response rate for targeted elimination diets was presented. Nonetheless, a significant limitation in pooling these results involves the degree of inconsistencies of the different testing techniques used in various studies (eg, skin-prick testing, atopy path tests, serum-specific IgE or Ig4 testing). Based on these heterogeneous and poor efficacy rates, the European and American guidelines advise against the use of allergy tests to identify causative food triggers in EoE and alternative medical or dietary therapies are advised.7Lucendo A. et al.United European Gastroenterol J. 2017; 5: 335-358Crossref PubMed Scopus (697) Google Scholar,8Dellon A. et al.Gastroenterology. 2018; 155: 1022-1033Abstract Full Text Full Text PDF PubMed Scopus (690) Google Scholar Last, another drawback on current dietary treatment is the lack of data on reintroduction of excluded foods and maintenance assessments, a topic that is only mentioned briefly in their discussion. In conclusion, the study provided a complete overview of current literature on dietary treatment in EoE. However, it would have been prudent for the authors to approach the presentation of their response rates with more caution, given the heterogeneity, modest quality, and predominantly retrospective nature of the included studies. Dietary treatment in EoE is eagerly awaited but without the ability to accurately identify the culprit food and without long-term remission rates, one could argue that dietary treatment in its current form is not yet a sustainable, nonpharmaceutical, long-term solution. Efficacy of Elimination Diets in Eosinophilic Esophagitis: A Systematic Review and Meta-analysisClinical Gastroenterology and HepatologyVol. 21Issue 9PreviewEosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of 4 major dietary treatment regimens in EoE, updating the evidence presented in a meta-analysis from 2014. Full-Text PDF Open AccessReplyClinical Gastroenterology and HepatologyVol. 22Issue 4PreviewWe would like to thank our colleagues for their valuable contributions to the discussion.1 Considering their first argument that response rates may be overestimated, it is certainly true that the high degree of heterogeneity, as also mentioned in our limitations, restricts data quality. The same accounts for the high number of observational studies. Nevertheless, the remission rates identified in our analysis are comparable with a 2014 meta-analysis, in which Arias et al2 showed an even higher efficacy rate of 72.1 for the 6-food elimination diet and 45.5% for the targeted elimination diet (TED). Full-Text PDF